19-1880054-T-G

Variant names:

• chr19-1880054-T-G
• NM_001130111.2:c.394A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130111.2(ABHD17A):​c.394A>C​(p.Ile132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ABHD17A NM_001130111.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236

Genes affected

ABHD17A (HGNC:28756): (abhydrolase domain containing 17A, depalmitoylase) Enables palmitoyl-(protein) hydrolase activity. Involved in protein depalmitoylation and protein localization to membrane. Located in endosome membrane; nuclear speck; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10257441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD17A	NM_001130111.2	c.394A>C	p.Ile132Leu	missense_variant	Exon 3 of 5	ENST00000292577.12	NP_001123583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD17A	ENST00000292577.12	c.394A>C	p.Ile132Leu	missense_variant	Exon 3 of 5	1	NM_001130111.2	ENSP00000292577.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460802 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726720

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.011	T;.;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.85	N;N;.
REVEL	Benign	0.018
Sift	Benign	0.37	T;T;.
Sift4G	Benign	0.57	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.33
MutPred		0.43		Gain of loop (P = 0.0312);.;.;
MVP		0.44
ClinPred		0.091	T
GERP RS		2.2
Varity_R		0.076
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1880053;